Dear Editor,
The current pandemic has propelled an exceptional partnership between governments and the scientific community to identify innovative and effective solutions to tackle the burden of the novel coronavirus SARS‐CoV‐2. Since 2020, numerous vaccines have been rolled out 1 : DNA vaccines, mRNA vaccines, nonreplicating viral vector vaccines, inactivated vaccines, live attenuated vaccines, subunit vaccines and trained immunity‐based vaccines are now available in many countries.
Despite the effectiveness and good safety profiles of COVID‐19 vaccines, researchers from different parts of the world have reported the onset of cutaneous adverse reactions following their inoculation. 2 Local injection site reactions, pityriasis rosea‐like eruptions, pernio‐like reactions, morbilliform rashes, herpes zoster, urticaria, eczematous dermatitis and autoimmune bullous reactions are examples of the skin manifestations which have been described in the medical literature after the vaccination. 2 Moreover, flare events were observed in people with chronic dermatological conditions like hidradenitis suppurativa, psoriasis, atopic dermatitis and acne. 2 , 3
We reviewed the PubMed (MEDLINE) database to identify the articles that have described the appearance of female genital mucosal lesions following the administration COVID‐19 vaccines.
We identified seven studies which reported the appearance of female mucosal findings after the inoculation of COVID‐19 vaccines (Table 1).
TABLE 1.
Female genital mucosa lesions associated with COVID‐19 vaccines
| Author, year | Country/region | Age (years) | Vaccine type | Latency after vaccination (days) | Treatment | Genital mucosa finding | Detailed description of genital findings | Comorbidities | Time to resolution |
|---|---|---|---|---|---|---|---|---|---|
| Salusti‐Simpson et al., 6 2022 | USA | 22 | BNT162b2 booster vaccine | 2 | Prednisone, clobetasol ointment, mupirocin ointment | Acute vulvar ulcers | Vulvar edema and extensive ulceration bilaterally, with yellow, grey purulent drainage and pseudomembrane | History of oral aphthous ulcers and 2 previous episodes of acute vulvar ulcers | Improvement in discomfort after 3 weeks |
| Wojcicki et al., 7 2022 | USA | 16 | Second dose of BNT162b2 vaccine | 1 | Topical clobetasol, ibuprofen, acetaminophen, oral norethidrone | Vulvar ulcers | Well demarcated ulcerated lesion with adherent yellow and grey fibrinous exudate and a necrotic‐appearing border. Desquamation of the surrounding tissue | Soft palate cleft, club foot, syndactyly of her left foot, and congenital hearing impairment in the right ear, history of recurrent oral ulcerations | Improvement in symptoms at 2 weeks follow‐up |
| Hsu et al., 10 2022 | USA | 12 | Second dose of BNT162b2 vaccine | 2 | Topical clobetasol ointment, lidocaine jelly, oral acetaminophen, ibuprofen | Vulvar ulcers | Well‐circumscribed, shallow ulcers with yellowish sloughing and purulent exudate, labial edema | None | Complete healing after 2 weeks |
| USA | 14 | Second dose of BNT162b2 vaccine | 3 | Clobetasol ointment, lidocaine gel, ibuprofen, oral nortriptyline, oral prednisone | Vulvar ulcers | Labial swelling, labial ulcers with overlying grey eschar | History of genital ulceration | Almost complete ulcer resolution after 4 weeks | |
| USA | 29 | First and second doses of Moderna SARS‐CoV‐2 vaccine | 1 (after 1st dose) and 2 (after 2nd dose) | Clobetasol ointment | Vulvar ulcers | Erythematous erosions | Recurrent genital ulcers, asthma, recurrent oral aphthous ulcers | Complete resolution (time not reported) | |
| Wijaya et al., 11 2022 | Australia | 16 | Second dose of the BNT162b2 vaccine | 4 | Oral prednisolone | Vulvar aphthosis | Multiple well‐demarcated vulvar ulcers with yellow‐grey exudate | None | No symptoms at 4‐week follow‐up |
| Australia | 14 | Second dose of the BNT162b2 vaccine | 5 | Oral prednisolone | Vulvar aphthosis | Vulvar ulcers and edema | Medical history of monthly oral ulcers | Full resolution at 1‐week follow‐up | |
| Australia | 19 | First dose of AstraZeneca (Vaxzevria) ChAdOx1 nCoV‐19 vaccine | 3 | Ibuprofen | Vulvar aphthosis | Mild vulvar aphthosis | None | Full resolution at 1‐week follow‐up | |
| Drucker et al., 12 2022 | USA | 14 | Second dose of the BNT162b2 vaccine | 2 | Topical lidocaine | Vulvar aphthous ulcers | Purple‐pink shallow‐based ulcerations with sloughing yellow roof at the core and surrounding edema | Type I von Willebrand disease | Ulcer resolution after 10 days |
| González‐Romero et al., 4 2021 | Spain | 24 | AstraZeneca vaccine (dose not specified) | 3 | Prednisone and analgesics | Acute noninfectious genital ulcer | Ulcers with an erythematous border and a fibrinous, nonsuppurative centre | Vulvar ulcers 9 months earlier | Complete resolution after 3 weeks |
| Europe | 18 | AstraZeneca vaccine (dose not specified) | 1 | Not reported | Acute noninfectious genital ulcer | Not reported | None | Not reported | |
| Europe | 25 | AstraZeneca vaccine (dose not specified) | 2 | Not reported | Acute noninfectious genital ulcer | Not reported | None | Not reported | |
| Europe | 24 | AstraZeneca vaccine (dose not specified) | 1 | Not reported | Acute noninfectious genital ulcer | Not reported | None | Not reported | |
| Europe | 25 | AstraZeneca vaccine (dose not specified) | 2 | Not reported | Acute noninfectious genital ulcer | Not reported | None | Not reported | |
| Popatia et al., 13 2022 | USA | 12 | Second dose of the BNT162b2 vaccine | 2 | Lidocaine jelly, triamcinolone ointment, acetaminophen, ibuprofen | Vulvar aphthous ulcer | Ulcers with a red rim and a white‐grey necrotic crust | None | Complete resolution after 10 days |
According to the data that were retrieved from our literature search, 15 patients (mean age = 18.9 ± 5.3 years) developed reactive nonsexually related genital ulcers after the administration of mRNA vaccines (60%) and the AstraZeneca (Vaxzevria) ChAdOx1 nCoV‐19 vaccine (40%). Genital mucosa complications were reported the most after the second dose of the BNT162b2 mRNA vaccine (47%; mean latency time = 2.7 days). On the other hand, for what concerns the AstraZeneca vaccine (mean latency time = 2 days), in five cases the dose after which the genital lesions appeared was not reported. 4
The only vaccine types which have been described to be associated with genital mucosa lesions in women are part of the mRNA and vector vaccine families. We may speculate that this could be traced back to the tendency of physicians to not publish about mild cases. Moreover, this could be explained by the reluctance of patients to seek medical advice when intimate areas of the body are affected by what might be perceived as unaesthetic lesions or the manifestation of sexually transmitted infections.
The vulvar ulcers described resolved in most instances with or without the aid of symptomatic treatment.
Nonsexually transmitted genital ulcers have been reported in association to COVID‐19 and cytomegalovirus in the medical literature. 5 The mechanism behind nonsexually related vulvar ulcers associated with COVID‐19 vaccines is yet to be determined, however, Salusti‐Simpson et al. 6 endeavoured to hypothesize that such lesions may be the consequence of a type III hypersensitivity mechanism triggered by vaccines which leads to microvascular damage.
Wojcicki et al. 7 have observed that COVID‐19 vaccines may be associated with an exaggerated immune response in people who have a predisposition to oral and/genital ulcers thus causing flare‐ups. Of note, the host response involved in the genesis of mucosal ulcers appears to be polarized toward T helper 1 lymphocytes. 8 However, it appears plausible that an innate immune component may be involved in their pathogenesis as well. 9
All in all, this short review summarized the evidence describing the genital mucosa lesions detected in association to the inoculation of COVID‐19 vaccines. No causal relationship has been confirmed yet, but the close temporal relationship between the two suggests the existence of some type of link which connects genital lesions to SARS‐CoV‐2 vaccines, especially in people with predisposing risk factors.
FUNDING INFORMATION
None.
CONFLICT OF INTEREST
Dr Tammaro, Dr Kulakowska, Dr Cantisani, Dr Parisella, Dr Scarabello and Dr Adebanjo have nothing to declare.
DATA AVAILABILITY STATEMENT
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.
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Data Availability Statement
Data sharing not applicable to this article as no datasets were generated or analysed during the current study.